text: Clores recent work has focused on developing new NMR methods (such as paramagnetic relaxation enhancement, dark state exchange saturation transfer spectroscopy and lifetime line broadening) to detect, characterize and visualize the structure and dynamics of sparsely-populated states of macromolecules, which are important in macromolecular interactions but invisible to conventional structural and biophysical techniques. Examples of include the direct demonstration of rotation-coupled sliding and intermolecular translocation as mechanisms whereby sequence-specific DNA binding proteins locate their target site(s) within an overwhelming sea of non-specific DNA sequences; the detection, visualization and characterization of encounter complexes in protein-protein association; the analysis of the synergistic effects of conformational selection and induced fit in protein-ligand interactions; and the uncovering of "dark", spectroscopically invisible states in interactions of NMR-visible proteins and polypeptides (including intrinsically disordered states) with very large megadalton macromolecular assemblies. The latter includes an atomic-resolution view of the dynamics of the amyloid-β aggregation process. and the demonstration of intrinsic unfoldase/foldase activity of the macromolecular machine GroEL. These various techniques have also been used to uncover the kinetic pathway of pre-nucleation transient oligomerization events and associated structures involving the protein encoded by huntingtin exon-1, which may provide a potential avenue for therapeutic intervention in Huntingtons disease, a fatal autosomal dominant, neurodegenerative condition.